Organoselenides as potential immunostimulants and inducers of interferon gamma and other cytokines in human peripheral blood leukocytes

Abstract

A number of organoselenium compounds have been described as anti-inflammatory, antioxidant, glutathione peroxidase-like agents and inhibitors of prostaglandin synthesis. Here we report that bis [2-(N-phenyl-carboxamido)]phenyl diselenide, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (Ebselen) and related compounds are inducers of interferon gamma (IFN-gamma) and tumor necrosis factor (TNF) in human peripheral blood leukocytes. The IFN and TNF response was rapid, occurring within 20 h, and high--up to 1000 and 2000 units ml-1--and was clearly related to the dosage and the structure of the compounds. The action of the compounds and phytohemagglutinin was synergistic. The IFN gamma and TNF production was reduced after removing adherent cells. Although the mode of action of the compounds is not known, they appear to interact directly or indirectly with both adherent and non-adherent leukocytes, and stimulate the synthesis of a set of different cytokines including factors controlling the cell proliferation. Therefore, organoselenides may be regarded as the biological response modifiers.

Antioxidant Activity of the Anti‐Inflammatory Compound Ebselen: A Reversible Cyclization Pathway via Selenenic and Seleninic Acid Intermediates

“…[12] Ebselen also exhibits significant antitumor and immunomodulating activities and has been suggested to have a potential to protect ROS-mediated brain damage. [13] Interestingly, most of the biological activities of ebselen have been associated with its ability to mimic the enzymatic properties of glutathione peroxidase (GPx), a mammalian selenoenzyme that protects various organisms from oxidative damage by catalyzing the reduction of harmful hydroperoxides in the presence of glutathione (GSH) (Scheme 1) or other thiol cofactor systems. [14] In addition to the GPx activity, ebselen has been shown to enhance the antioxidant activity of the human thioredoxin (Trx) system by acting as a substrate for the selenium-containing enzyme, thioredoxin reductase (TrxR).…”

New Organoselenium Compounds Active against Pathogenic Bacteria, Fungi and Viruses

“…[4][5][6] In our previous papers we reported that various 2-substituted benzisoselenazol-3(2H)-ones and related diaryl diselenides exhibited high activity as immunostimulants inducing cytokines such as interferon, tumor necrosis factor and interleukin (IL-2) in human peripheral blood leukocytes. 7,8) Moreover, some of these compounds, particularly their 7-azaanalogues, exhibited high inhibitory activity against pathogenic bacteria, fungi and viruses. 9) In this paper we report synthesis, chemical properties as well as inhibitory activity against viruses, bacteria and fungi of ebselen analogues (2-6), having in 2-position alkyl groups (2) or containing oxaalkyl or azaalkyl functions (3)(4)(5)(6).…”

A novel and facile one-pot synthesis of pyridylselenium compounds through selective bromine–magnesium exchange with isopropylmagnesium halide

“…This is due to a cumulative electron-withdrawing influence of the SeCBr 3 group at the 3 . This may be attributed to the fact that the more polarizable bromine atom can more effectively polarize the electron density at the selenium atom, thus causing deshielding in the 77 Se resonance.…”